Uncovering the genetic basis of diarrhoea

In the realm of biomedical research, understanding the genetic causes of diseases has been a longstanding pursuit. Diseases such as Huntington's, sickle cell anaemia, and muscular dystrophy have been linked to mutations in single genes, providing valuable insights into the intricate relationship between genetics and health. However, for most diseases, the picture is more complex, involving variations across multiple genes and environmental factors. Genome-wide association studies (GWAS) have emerged as a powerful tool to explore the genetic underpinnings of various diseases. These studies compare the genetic makeup of individuals with a particular condition, such as diarrhoeal diseases, to those without, identifying key genetic variants associated with susceptibility or protection.

Bangladesh's role in diarrhoeal disease research:

Bangladesh, a country grappling with endemic diarrhoeal pathogens like Rotavirus, Shigella, and Vibrio cholerae, has become a focal point for groundbreaking genetic studies. Researchers from ICDDR,B, in collaboration with others, have utilised three birth cohorts to investigate the genetic variants influencing susceptibility to diarrheal diseases. These cohorts, namely the Dhaka Birth Cohort, PROVIDE, and Cryptosporidiosis Birth Cohort, provide valuable genome-wide data and stool samples for surveillance.

Recent discoveries in genetic variants:

A study published in the Journal of Infectious Diseases in March 2023 delved into the influence of genetic variation on the frequency and duration of diarrhoea in infants. Identifying three protective variants, the study shed light on genomic regions related to intestinal inflammation and the control of intestinal blood flow. Earlier studies by the same group revealed genetic variants associated with Shigella-associated diarrhoea and Entamoeba histolytica infection. These findings contribute to understanding the biological mechanisms that underlie susceptibility to different infectious diseases, offering potential avenues for novel therapeutics.

The evolutionary puzzle: Why do these variants exist?

The diversity in individual responses to diarrhoeal pathogens suggests a complex interplay between genetics and environmental factors. It's possible that pathogens have exerted strong selection on human populations, favouring the spread of variants that provide protection. This notion is supported by the 2013 study on cholera, which identified variants associated with susceptibility and underwent strong past selection in the Bangladeshi population.

Colistin resistance: A growing public health concern:

In a recent development, researchers uncovered the presence of Colistin-resistant Escherichia coli (E. coli) in Dhaka city sludge, a last-resort antibiotic widely used in the poultry industry in Bangladesh. This multidrug-resistant bacterium, resistant to 11 antibiotics, carries the mcr-1 gene—an alarming indication of antibiotic resistance. Overuse of Colistin in poultry farms, estimated at 30 percent in Bangladesh, contributes to the rise of multidrug-resistant bacteria. Urban sludge disposal into water bodies further amplifies the environmental presence of antibiotics, posing a serious threat to humans and animals.

The one health approach:

The interconnectedness of human, animal, and environmental health underscores the need for a one-health approach. Widespread faecal-oral contamination, coupled with antibiotic residues entering the food chain, intensifies the risk of rapid transmission of multidrug-resistant pathogens. The study strongly advocates broader surveillance in both clinical and environmental settings to prevent the further spread of bacteria carrying mcr-1. It calls for urgent measures to ensure rational antibiotic usage, monitoring of clinical settings, and proper disposal systems to safeguard against the looming threat of antibiotic resistance.

As we navigate the intricate landscape of genetics, infectious diseases, and antibiotic resistance, these discoveries emphasise the urgency of responsible antibiotic use and environmental stewardship. Our actions today will determine our ability to combat diseases in the future.